Phosphonylation of organic compounds and polymers has been documented in the prior art. Early applications focused on mass phosphonylation of non-functional polymers to introduce phosphonylate groups randomly along their carbon chain by allowing a solution of these polymers in phosphorous trichloride to interact with gaseous oxygen (U.S. Pat. Nos. 3,097,194; 3,278,464). For example, U.S. Pat. No. 3,097,194 to Leonard is directed to a process for preparing elastomeric phosphonylated amorphous copolymers of ethylene and propylene which are essentially free of low molecular weight polymer oils. Phosphorylation, or esterification of the copolymer, is conducted in situ of the copolymer solution mass after inactivating a polymerization catalyst with water and oxygen to convert the catalyst to an inert metal oxide. Oxygen is then bubbled through the reaction mass in the presence of phosphorous trichloride to obtain the phosphorylated copolymer.
An example of phosphonated polymers is provided in U.S. Pat. No. 3,278,464 to Boyer et al. In accordance therewith, ethylenically unsaturated polymers are reacted with an organic-substituted phosphorous compound to produce phosphonated polymers. Like the process described above, attachment of the phosphorous groups results in near-homogeneous, or mass, phosphonylation within the polymer and phosphorous compounds are combined in a solvent system.
Moreover, in U.S. Pat. No. 4,207,405 to Masler et al., polyphosphates are provided that are the homogeneous reaction products, in an organic solvent, of phosphorous acid or phosphorous trichloride and a water-soluble carboxyl polymer. U.S. Nat. Nos., 3,069,372 to Schroeder et al., U.S. Pat. No. 4,678,840 to Fong et al., U.S. Pat. No. 4,774,262 to Blanquet et al., U.S. Pat. No. 4,581,415 to Boyle Jr., et al., and U.S. Pat. No. 4,500,684 to Tucker show various phosphorous-containing polymer compounds.
U.S. Pat. Nos. 4,814,423 and 4,966,934 to Huang et al., describe adhesives for bonding polymeric materials to the collagen and calcium of teeth. For bonding to calcium, the adhesive employs an ethylenically unsaturated polymeric monophosphate component. A tooth is coated with the adhesive and then a filling is applied.
More recently, restricting the phosphonylation to the surface of polymeric substrates was achieved to produce articles with surface-phosphonylate functionalities and practically intact bulk (U.S. Pat. Nos. 5,491,198 and 5,558,517 to Shalaby et al.). This was achieved by gas phase phosphonylation of a preformed article with PCl3 and O2 or passing through a solution of PCl3 in a non-reactive organic liquid that is also a non-solvent for the polymeric article. In effect, a process for phosphonylating the surface of an organic polymeric preform and the surface-phosphonylated preforms produced thereby are provided. Organic polymeric preforms made from various polymers including polyethylene, polyether-ether ketone, polypropylene, polymethyl methacrylate, polyamides and polyester, and formed into blocks, films, and fibers may have their surfaces phosphonylated according to that process. The process involves the use of a liquid medium that does not dissolve this organic polymeric preform but does dissolve a phosphorous halide such as phosphorous trichloride, and the like. The process allows for surface phosphonylation of the organic polymeric preform such that up to about 30 percent but preferably up to about 20 percent, of the reactive carbon sites in the polymer are phosphonylated. The phosphonylated organic polymers are particularly useful as orthopedic implants because hydroxyapatite-like surfaces which can be subsequently created on the organic implants allow for co-crystallization of hydroxyapatite to form chemically bound layers between prosthesis and bone tissue.
Although various phosphonylated polymers are known, the prior art is deficient in affording phosphorous-containing groups randomly and covalently attached to carbon atoms of aliphatic chains and pendant side groups of organo-soluble polymers such as polyalkylene oxides, polyamides, polyesters, and acrylate polymers, that are tailored for use in specified technology areas.
In one aspect the present invention is directed to a randomly phosphonylated acrylate polymeric composition which includes an acrylic polymer and phosphorous-containing functional groups, wherein the phosphorous atom of each functional group is covalently bonded to a carbon atom of the acrylic polymer and wherein the phosphorous atoms comprise at least about 0.1 percent by weight of the polymeric composition.
Preferably, the acrylic polymer is polymethyl-methacrylate and the phosphorous atoms comprise at least 0.5 percent by weight of the polymeric composition. Optionally, the acrylic polymer is based on methyl-methacrylate and methacrylic acid repeat units. It is also within the scope of the present invention that the acrylic polymer includes at least one polymerizable side group per chain, preferably a group derived from a bis-acrylate monomer, most preferably, ethylene bis-methacrylate.
A preferred application for the phosphonylated acrylate polymeric composition of the present invention is as a dental product such as a varnish or sealer, preferably one which includes fluoride ions which may be released on a controlled manner. It is also desirable that the dental product made in accordance with the present invention includes bioactive compounds such as antimicrobials, anti-inflammatory drugs, or pain-relieving agents, with the polymeric composition being capable of regulating the release of the bioactive compounds.
In another aspect the present invention is directed to a randomly phosphonylated polyalkylene oxide polymeric composition which includes a polyalkylene oxide polymer and phosphorous-containing functional groups, wherein the phosphorous atom of each of the functional groups is covalently bonded to a carbon atom of the polyalkylene oxide polymer and wherein the phosphorous atoms comprise at least about 0.1 percent by weight of the polymeric composition. Preferably the alkylene group of the polyalkylene oxide polymer has from two to six carbon atoms.
In yet another aspect the present invention is directed to a randomly phosphonylated polyamide composition which includes a polyamide polymer and phosphorous-containing functional groups, wherein the phosphorous atom of each of the functional groups is covalently bonded to a carbon atom of the polyamide polymer and wherein the phosphorous atoms comprise at least about 0.1 percent by weight of the composition. Preferably, the polyamide is the polymerization product of N-alkyl laurolactam.
In a still further aspect the present invention is directed to a randomly phosphonylated polyester composition which includes a polyester polymer and phosphorous-containing functional groups, wherein the phosphorous atom of each of the functional groups is covalently bonded to a carbon atom of the polyester polymer and wherein the phosphorous atoms comprise at least about 0.1 percent by weight of the composition. Preferably the polyester is poly-68-caprolactone. The present polyester composition is especially useful as a flame retardant additive for polyesters and polyurethanes.
All of the present inventive polymeric compositions may include a bioactive compound linked to the phosphonyl functionality.
The present invention deals with novel phosphonylated derivatives of polyalkylene oxides, N-substituted aliphatic polyamides, and acrylate polymers, and preferably, specifically, polyethylene oxide (PEO), N-ethyl, Nylon 12 (N-12) [description of alkylated N-12 can be found in Shalaby et al., J. Polym. Sci.-Polym. Phys.Ed., 11,939 (1973)], and polymethyl methacrylate (PMMA). Generally, the phosphonylation of the representative members of these groups of polymers occurs by bubbling oxygen through a polymer solution in PCl3 with or without a non-reactive organic solvent. The resulting phosphonyldihalide-bearing polymers may then be converted to corresponding phosphonic acid and its metal salts, amides, imides, or esters. Conversion to (1) phosphonic acid is achieved by reacting with water in the presence or absence of an acidic or basic catalyst (followed by acidification); (2) amides by reacting with an amine; (3) imides by reacting with a primary or secondary amide (as in the case of the sodium salt of xcex5-caprolactam); and (4) esters by reacting with an alcohol or phenol.
A preferred composition of the present invention is a phosphonylated PMMA having more than 0.1 percent phosphorous, present as phosphonic acid functionality, with the phosphonic acid being the dominant phosphonyl functionality. Another preferred composition of this invention is a derivative of the phosphonylated PMMA wherein the methyl ester groups of PMMA are partially or fully hydrolyzed [that take place during the hydrolysis of xe2x80x94P(O)Cl2 to P(O)(OH)2] are reacted (esterified) with a glycidyl acrylate (such as glycidyl methacrylate) to introduce a polymerizable acrylic side group onto the phosphonylated PMMA (PPMMA) chain. Another preferred composition of this invention is the reaction product of the PMMA [through the xe2x80x94P(O)Cl2 functionality] with hydroxyethyl methacrylate (through the xe2x80x94OH group) to yield a product (PMH) having a phosphonate ester side group with a polymerizable acrylic functionality. Another preferred composition of this invention is a phosphonylated polyethylene oxide (OPPO) having more than 0.1 percent phosphorous present primarily as phosphonic acid groups, phosphonyl dichloride and their respective derivative with hydroxy- or amine-bearing bioactive compounds. Another preferred composition of this invention is a phosphonylated N-alkylated Nylon 12 and more preferably N-ethyl Nylon 12 having more than 0.1 percent phosphorous present primarily as phosphonic acid. Another preferred composition of this invention is a derivative of the phosphonylated N-ethyl Nylon-12, wherein the initial phosphonyl dihalide groups are reacted with sodium xcex5-caprolactam [using a similar process to that described by Shalaby and Reimschuessel, J. Polym. Sci.-Polym. Chem. Ed., 15, 1349 (1977)]. Another preferred composition of this invention is phosphonylated polyester and more preferably poly-xcex5-caprolactone having more than 0.1 percent P as free phosphonic acid or dialkyl phosphonate groups. The latter can be prepared by reacting the initial phosphonylation product bearing phosphonyl dihalide groups with an alcohol such as ethanol or methanol.
Of the many possible applications of the new compositions subject of this invention, the following are representative systems:
1. Phosphonylated PMMA and Derivativesxe2x80x94These can be used in several dental applications pertinent to (a) desensitizing through interaction with Ca+2 in the biologic environment to seal the teeth surface and fill the micro-channel with an insoluble polymeric salt; (b) increasing the impact strength of dental fillers through ionic binding of the polymeric chain that acts as an impact modifier; (c) increasing the impact strength of cement ionomers through the ionic binding of the impact modifying polymer; (d) pretreating the surface of dentine for improved adhesion to dental filling; (e) surface-coating to provide an adherent dental varnish or a controlled release system for fluorides and other dental agents for treating infections (including microbial ones) or pain; and (f) interfacial-bonding of phosphonylated fibers to a methacrylate-based matrix for producing high impact dental composites.
2. Phosphonylated Polyethylene Oxides (PEO) and Derivativesxe2x80x94These can be used as drug carriers in different controlled release systems, such as those used in transdermal delivery with or without employing an iontophoretic scheme. Other uses of the PEO phosphonic acid derivatives can include those pertinent to cold sterilization and disinfection. Phosphonylated derivatives bearing phosphonyl dihalide groups can be used for covalently binding hydroxy- and/or amine-bearing bioactive compounds for their controlled release. Yet another application of phosphonic acid derivatives include their use as polyelectrolytes for flocculation. The phosphonic acid-bearing system can be used as a carrier of cationic drugs for controlling their release in oral, intranasal, intravaginal, or transdermal pharmaceutical formulations. The phosphonylated PEO can be used as a foam for protecting flammable objects exposed to an open flame.
3. Phosphonylated N-ethyl Nylon 12 and Derivativesxe2x80x94N-ethyl Nylon 12 with practically all the phosphonyl moieties present as phosphonic acid groups can be used as polymeric catalysts for the hydrolytic polymerization of lactams. The derivatives of the phosphonylated polymer carrying N-substituted xcex5-caprolactam group can be used as a co-catalyst for the anionic polymerization of lactams into comb-shaped or crosslinked structures.
4. Phosphonylated Poly-xcex5-Caprolactone and Its Derivativesxe2x80x94These can be used as primers for metallic fibers in polymeric composite applications. The alkyl-phosphonate groups can be used as flame-retarding additives for polyesters and polyurethanes.
Specific examples for the preparation of representative compositions are given below.